Lichens are similar to non-flowering plants and refer to the symbiotic association of a fungus (mycobiont) and an alga (photobiont) and/or cyanobacteria. In lichens, the fungus forms a thallus or lichenized stroma that contains characteristic secondary metabolites (Ahmadjin V., The lichen symbiosis, Wiley, New York, pp. 1-6, 1993). It is difficult to obtain sufficient amounts of natural lichen samples, and technology of cultivating large amounts of lichens is not known. For this reason, studies on lichens were insufficient compared to studies on higher plants.
As the tissue culture method, mass-production method and biological analysis method for lichens have been improved, studies thereon have been actively conducted (Behera, B. C. et al., Lebensm. Wiss. Technol., 39:805, 2006). Compounds having various biological activities (including cytotoxicity, antifungal, antimicrobial and antioxidant activities), including fatty acids, depsides, depsidones, dibenzofurans, diterpenes, anthraquinones, naphtoquinones, usninic acid, pulvinic acids, xanthones, and epidithiopiperazinediones, have been isolated from lichens (Muller, K., Appl. Microbiol. Biotechnol., 56:9-16, 2001).
Ramalina terebrata is a lichen that grows naturally in the Antarctic King George Island and can be easily collected from the King George Island. During studies on the Antarctic lichen Ramalina terebrata, the present inventors previously have isolated the novel compound ramalin having excellent antioxidant activity (Korean Patent Laid-Open Publication No. 10-2010-0052130). In addition, it has been reported that ramalin has excellent anti-inflammatory activity (Korean Patent Laid-Open Publication No. 10-2010-0052551).
Because ramalin was confirmed to have excellent antioxidant and anti-inflammatory activities, there is a need to produce ramalin in large amounts. However, a conventional method of isolating ramalin from Ramalina terebrata using methanol (Korean Patent Laid-Open Publication No. 10-2010-0052130) entails a problem in that the production of ramalin is expensive and time-consuming, because of the slow growth rate of the polar lichen and because it is difficult to collect a large amount of the polar lichen in nature and the amount of ramalin extracted from Ramalina terebrata is very small. Further, ramalin is easily decomposed due to its high antioxidant activity. In addition, ramalin is difficult to maintain, because it is so unstable that more than half thereof disappears within 4 days at room temperature.
L-glutamic acid is a kind of amino acid which has been used as an amino acid-based seasoning, and it is commercially used as a dietary supplement, a nutrition enhancer, a flavor enhancer or the like as a substitute for salt. Thus, L-glutamic acid is inexpensive, can be obtained in large amounts and, at the same time, has optically active sites, like ramalin.
Accordingly, the present inventors have made extensive efforts to develop a method for chemically synthesizing ramalin, and as a result, have found that when L-glutamic acid having optically active sites, like ramalin, is allowed to react with 2-hydrazinylphenol, a ramalin exhibiting the same effects as those of a ramalin derived from a natural material is synthesized, and when the synthesized ramalin is stored together with vitamin C, it is prevented from being decomposed so that it can be maintained for a long period of time, thereby completing the present invention.